A novel synaptopathy-defective synaptic vesicle protein trafficking in the mutant CHMP2B mouse model of frontotemporal dementia

Mutations in the ESCRT-III subunit CHMP2B cause frontotemporal dementia (FTD) and lead to impaired endolysosomal trafficking and lysosomal storage pathology in neurons. We investigated the effect of mutant CHMP2B on synaptic pathology, as ESCRT function was recently implicated in the degradation of synaptic vesicle (SV) proteins. We report here that expression of C-terminally truncated mutant CHMP2B results in a novel synaptopathy. This unique synaptic pathology is characterised by selective retention of presynaptic SV trafficking proteins in aged mutant CHMP2B transgenic mice, despite significant loss of postsynaptic proteins. Furthermore, ultrastructural analysis of primary cortical cultures from transgenic CHMP2B mice revealed a significant increase in the number of presynaptic endosomes, while neurons expressing mutant CHMP2B display defective SV recycling and alterations to functional SV pools. Therefore, we reveal how mutations in CHMP2B affect specific presynaptic proteins and SV recycling, identifying CHMP2B FTD as a novel synaptopathy. This novel synaptopathic mechanism of impaired SV physiology may be a key early event in multiple forms of FTD, since proteins that mediate the most common genetic forms of FTD all localise at the presynapse

Implementing the model of human occupation across a mental health occupational therapy service: communities of practice and a participatory change process

The implementation of evidence-based change in practice settings is complex and far reaching, but only limited research has been undertaken in this area. This participatory action research study investigated the implementation of the Model of Human Occupation (MOHO) across a mental health occupational therapy service. Method: The study involved preparatory workshops and 12 months of team-based, monthly group reflective supervision sessions, facilitated by a colleague from academia, with follow-up contact for a further 12 months. Findings: The main findings emphasise the importance of developing a critical learning space, or 'community of practice', and identify that barriers to theory implementation can be overcome by collective effort with a shared dialectic. The successful development of a community of practice required the careful consideration of a number of interconnected influences, including those of self, peer and facilitator, and contextual and theoretical relationships. Conclusion: The study concluded that the community of practice was central in supporting the effective implementation of MOHO and its associated assessment tools. A key output of the study is a Participatory Change Process, which illustrates the key steps undertaken and interrelated factors affecting theory uptake. The process requires further testing, but has potential to guide theory implementation in other settings. © The College of Occupational Therapists Ltd

Dynamin I phosphorylation by GSK3 controls activity-dependent bulk endocytosis of synaptic vesicles.

Glycogen synthase kinase 3 (GSK3) is a critical enzyme in neuronal physiology; however, it is not yet known whether it has any specific role in presynaptic function. We found that GSK3 phosphorylates a residue on the large GTPase dynamin I (Ser-774) both in vitro and in primary rat neuronal cultures. This was dependent on prior phosphorylation of Ser-778 by cyclin-dependent kinase 5. Using both acute inhibition with pharmacological antagonists and silencing of expression with short hairpin RNA, we found that GSK3 was specifically required for activity-dependent bulk endocytosis (ADBE) but not clathrin-mediated endocytosis. Moreover we found that the specific phosphorylation of Ser-774 on dynamin I by GSK3 was both necessary and sufficient for ADBE. These results demonstrate a presynaptic role for GSK3 and they indicate that a protein kinase signaling cascade prepares synaptic vesicles for retrieval during elevated neuronal activity

Water induced sediment levitation enhances downslope transport on Mars

On Mars, locally warm surface temperatures (~293 K) occur, leading to the possibility of (transient) liquid water on the surface. However, water exposed to the martian atmosphere will boil, and the sediment transport capacity of such unstable water is not well understood. Here, we present laboratory studies of a newly recognized transport mechanism: “levitation” of saturated sediment bodies on a cushion of vapor released by boiling. Sediment transport where this mechanism is active is about nine times greater than without this effect, reducing the amount of water required to transport comparable sediment volumes by nearly an order of magnitude. Our calculations show that the effect of levitation could persist up to ~48 times longer under reduced martian gravity. Sediment levitation must therefore be considered when evaluating the formation of recent and present-day martian mass wasting features, as much less water may be required to form such features than previously thought

Role of Ucp1 enhancer methylation and chromatin remodelling in the control of Ucp1 expression in murine adipose tissue

Aims/hypothesis Increasing the expression of the brown adipose tissue-specific gene uncoupling protein-1 (Ucp1) is a potential target for treating obesity. We investigated the role of DNA methylation and histone modification in Ucp1 expression in adipose cell lines and ex vivo murine adipose tissues. Methods Methylation state of the Ucp1 enhancer was studied using bisulphite mapping in murine adipose cell lines, and tissue taken from cold-stressed mice, coupled with functional assays of the effects of methylation and demethylation of the Ucp1 promoter on gene expression and nuclear protein binding. Results We show that demethylation of the Ucp1 promoter by 5-aza-deoxycytidine increases Ucp1 expression while methylation of Ucp1 promoter–reporter constructs decreases expression. Brown adipose tissue-specific Ucp1 expression is associated with decreased CpG dinucleotide methylation of the Ucp1 enhancer. The lowest CpG dinucleotide methylation state was found in two cyclic AMP response elements (CRE3, CRE2) in the Ucp1 promoter and methylation of the CpG in CRE2, but not CRE3 decreased nuclear protein binding. Chromatin immunoprecipitation assays revealed the presence of the silencing DiMethH3K9 modification on the Ucp1 enhancer in white adipose tissue and the appearance of the active TriMethH3K4 mark at the Ucp1 promoter in brown adipose tissue in response to a cold environment. Conclusions/interpretation The results demonstrate that CpG dinucleotide methylation of the Ucp1 enhancer exhibits tissue-specific patterns in murine tissue and cell lines and suggest that adipose tissue-specific Ucp1 expression involves demethylation of CpG dinucleotides found in regulatory CREs in the Ucp1 enhancer, as well as modification of histone tails

Crop Updates 2006 - Oilseeds

This session covers thirteen papers from different authors: 1. INTRODUCTION, Graham Walton, CONVENOR, Department of Agriculture 2. The performance of new TT canola varieties in National Variety Testing (NVT) WA, Fiona Martin, Research Agronomist, Agritech Crop Research 3. Comparison of TT Canola Varieties in Oilseeds WA Trials – 2005, Collated by G.H. Walton, Department of Agriculture, WA, from a collaboration between Oilseeds WA, Seed Companies, Agronomists and Growers 4. An overview of the potential for a Biofuels Industry in Western Australia, Anne Wilkins and Nathan Hancock, Department of Agriculture 5. Retrieval of fertile progeny from interspecific crosses between Brassica napus and B. carinata using microspore culture, Matthew Nelson, Marie-Claire Castello, Linda Thomson, Anouska Cousin, Guijun Yan and Wallace Cowling; School of Plant Biology (M084), The University of Western Australia 6. Advances in canola blackleg epidemiology and its implication in understanding and managing the disease, Moin Salam, Bill MacLeod, Ravjit Khangura, Jean Galloway and Art Diggle, Department of Agriculture 7. Effect of fertiliser phosphorus and nitrogen on grain yields and concentration of oil and protein of canola grain, R.F. Brennan, M.D.A. Bolland, Department of Agriculture 8. Effect of applying fertiliser potassium and nitrogen on canola grain yields and concentration of oil and protein in grain, R.F. Brennan, M.D.A. Bolland, Department of Agriculture 9. Effect of fertiliser nitrogen and sulfer on canola yields and concentration of oil in grain, R.F. Brennan, M.D.A. Bolland, Department of Agriculture 10. Uptake of K from topsoil and subsoil by canola, P.M. Damon and Z. Rengel, Faculty of Natural and Agricultural Sciences, The University of WA 11. Accumulation of P and K by canola plants, Terry Rose, Zed Rengel and Qifu Ma, Faculty of Natural and Agricultural Sciences, The University of WA 12. Varied response from applying nitrogen at late flowering in canola! Dave Eksteen, Agronomist, United Farmers Cooperative 13. To investigate the timing, rate and placement of nitrogen on canola – Jerdacuttup 2005, Dave Eksteen, Agronomist, United Farmers Cooperativ